Mass spectrometry has been used to determine the extent of modification and the specific sites of modification on biomolecules. MS-based approaches have many advantages, including generally rapid analyses without radiolabeling. The MS analysis of protein-DNA crosslinks has been investigated using mass spectrometry. Products and digests have been analyzed by both positive and negative ion MALDI mass spectrometry and LC in combination with electrospray mass spectrometry. Additionally, products following crosslinking have been purified by SDS-PAGE and investigated by mass spectrometry. Free radicals are implicated in oxidative stress and are associated with a wide range of diseases and disorders. In this work, we have investigated the sites of radicals trapped by DMPO on deoxyribonucleosides and proteins using LC/MS/MS. With the addition of a cryo-electron microscopy (cryo-EM) facility, many PIs at NIEHS will be incorporating this technique into their studies. Publications show that this technique is often paired with crosslinking followed by mass spectrometric analyses. We are currently analyzing the use of the crosslinker BS3 with the proteins Grc3 and Las1 by mass spectrometry in collaboration with the Stanley laboratory to try to determine which residues from Grc3 and Las1 interact.